Host resistance to cancer almost certainly involves multiple immunospecific and non-specific mechanisms. Compelling in vitro evidence suggests an innate system of resistance involving macrophages and natural killer (NK) cells and emerging tumors provoke immune responses. Accordingly, the proposed experiments address a crucial issue: how do malignant cells in vivo evade destruction. The first experimental approach will examine the significance and causation of tumor related anti-inflammation. During the tenure of this award, we will (1) determine if an anti-inflammatory effect depresses natural resistance permitting tumor emergence by altering macrophage accumulation or NK cell function (2) examine whether tumors arising spontaneoulsy or after carcinogen induction alter monocytes and if the defect preceeds or follows tumor appearance, (3) look for a biphasic anti-inflammatory effect following tumor transplantation and determine (a) if the early phase depression correlates with tumor emergence and relates to soluble factors of viral, tumor, or host origin, and (b) if the late effect involves altered cell survival, and (4) investigate the kinetics of host cell accumulation and survival within tumors. The second approach will examine the means and relevance of macrophage control of cancer cells by defining and comparing cytotoxic and cytocidal activities in vitro and in vivo. New methods are proposed to distinguish between these activities and to evaluate overall effectiveness of macrophages on tumor progression or regression. Using these methods, we will (1) relate the bahavior of macrophages in vitro with their capacity for in vivo growth control, and (2) determine if isolated anti-inflammatory factors from tumor bearing hosts inhibit growth regulation. The proposed research focuses on the accumulation and function of macrophages within tumors.